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Discovery of new methylation markers to improve screening for cervical intraepithelial neoplasia grade 2/3

Overview of attention for article published in Clinical Epigenetics, March 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (79th percentile)
  • Good Attention Score compared to outputs of the same age and source (65th percentile)

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Title
Discovery of new methylation markers to improve screening for cervical intraepithelial neoplasia grade 2/3
Published in
Clinical Epigenetics, March 2016
DOI 10.1186/s13148-016-0196-3
Pubmed ID
Authors

A. Boers, R. Wang, R. W. van Leeuwen, H. G. Klip, G. H. de Bock, H. Hollema, W. van Criekinge, T. de Meyer, S. Denil, A. G J. van der Zee, E. Schuuring, G. B. A. Wisman

Abstract

Assessment of DNA promoter methylation markers in cervical scrapings for the detection of cervical intraepithelial neoplasia (CIN) and cervical cancer is feasible, but finding methylation markers with both high sensitivity as well as high specificity remains a challenge. In this study, we aimed to identify new methylation markers for the detection of high-grade CIN (CIN2/3 or worse, CIN2+) by using innovative genome-wide methylation analysis (MethylCap-seq). We focused on diagnostic performance of methylation markers with high sensitivity and high specificity considering any methylation level as positive. MethylCap-seq of normal cervices and CIN2/3 revealed 176 differentially methylated regions (DMRs) comprising 164 genes. After verification and validation of the 15 best discriminating genes with methylation-specific PCR (MSP), 9 genes showed significant differential methylation in an independent cohort of normal cervices versus CIN2/3 lesions (p < 0.05). For further diagnostic evaluation, these 9 markers were tested with quantitative MSP (QMSP) in cervical scrapings from 2 cohorts: (1) cervical carcinoma versus healthy controls and (2) patients referred from population-based screening with an abnormal Pap smear in whom also HPV status was determined. Methylation levels of 8/9 genes were significantly higher in carcinoma compared to normal scrapings. For all 8 genes, methylation levels increased with the severity of the underlying histological lesion in scrapings from patients referred with an abnormal Pap smear. In addition, the diagnostic performance was investigated, using these 8 new genes and 4 genes (previously identified by our group: C13ORF18, JAM3, EPB41L3, and TERT). In a triage setting (after a positive Pap smear), sensitivity for CIN2+ of the best combination of genes (C13ORF18/JAM3/ANKRD18CP) (74 %) was comparable to hrHPV testing (79 %), while specificity was significantly higher (76 % versus 42 %, p ≤ 0.05). In addition, in hrHPV-positive scrapings, sensitivity and specificity for CIN2+ of this best-performing combination was comparable to the population referred with abnormal Pap smear. We identified new CIN2/3-specific methylation markers using genome-wide DNA methylation analysis. The diagnostic performance of our new methylation panel shows higher specificity, which should result in prevention of unnecessary colposcopies for women referred with abnormal cytology. In addition, these newly found markers might be applied as a triage test in hrHPV-positive women from population-based screening. The next step before implementation in primary screening programs will be validation in population-based cohorts.

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Mendeley readers

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Geographical breakdown

Country Count As %
Netherlands 1 1%
United States 1 1%
Portugal 1 1%
Unknown 96 97%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 20 20%
Student > Ph. D. Student 13 13%
Student > Master 11 11%
Researcher 9 9%
Other 7 7%
Other 19 19%
Unknown 20 20%
Readers by discipline Count As %
Medicine and Dentistry 37 37%
Biochemistry, Genetics and Molecular Biology 17 17%
Agricultural and Biological Sciences 12 12%
Nursing and Health Professions 2 2%
Pharmacology, Toxicology and Pharmaceutical Science 2 2%
Other 8 8%
Unknown 21 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 8. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 September 2021.
All research outputs
#3,968,808
of 22,854,458 outputs
Outputs from Clinical Epigenetics
#253
of 1,256 outputs
Outputs of similar age
#61,856
of 300,116 outputs
Outputs of similar age from Clinical Epigenetics
#11
of 32 outputs
Altmetric has tracked 22,854,458 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,256 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one has done well, scoring higher than 79% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 300,116 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 79% of its contemporaries.
We're also able to compare this research output to 32 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.